Linked Life Data

15917222

Source:http://linkedlifedata.com/resource/pubmed/id/15917222

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2005-7-19
pubmed:abstractText
Circadian rhythms are controlled by the periodic accumulation of Period proteins, which act as transcriptional repressors of Clock-dependent genes. Period genes are themselves Clock targets, thereby establishing a negative transcriptional feedback circuit controlling circadian periodicity. Previous data have implicated the CK1epsilon isolog Doubletime (Dbt) and the F-box protein Slimb in the regulation of Drosophila Period (Per) through an unknown mechanism. In this work, we have identified components of the machinery involved in regulating the abundance of human Per1 in tissue culture cells. CK1epsilon and CK1gamma2 were found to bind to Per1 and to promote its degradation in an in vivo degradation assay. Per1 turnover was blocked by a dominant negative version of the Cul1 protein, a component of the SCF (Skp1-Cul1-F-box protein) ubiquitin ligase. We screened a panel of F-box proteins for those that would associate with Per1 in a CK1epsilon-dependent manner, and we identified beta-TRCP1 and beta-TRCP2, isologs of the Drosophila Slimb protein. RNA interference against beta-transducin repeat-containing protein (beta-TRCP) stabilizes endogenous and exogenous Per1. beta-TRCP associates with sequences near the N terminus of Per1 in a region distinct from the previously characterized CK1epsilon-binding site. beta-TRCP and CK1epsilon promote Per1 ubiquitination in vitro. Finally, RNA interference against beta-TRCP greatly decreases Clock-dependent gene expression in tissue culture cells, indicating that beta-TRCP controls endogenous Per1 activity and the circadian clock by directly targeting Per1 for degradation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/BTRC protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CLOCK Proteins, http://linkedlifedata.com/resource/pubmed/chemical/CLOCK protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/FBXW11 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PER1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Period Circadian Proteins, http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases, http://linkedlifedata.com/resource/pubmed/chemical/beta-Transducin Repeat-Containing...
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26863-72
pubmed:dateRevised
2011-3-11
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein.
pubmed:affiliation
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural